The goal of this study is to gather initial data regarding the potential of forced aerobic exercise to augment recovery of function in patients with stroke. Stroke, an endpoint of cardiovascular disease, is the leading cause of disability in the United States, and an estimated 5.8 million Americans are living with residual neurologic deficit due to stroke. Current approaches to stroke rehabilitation involve intensive, therapist-directed task practice that is both expensive and, in some cases, ineffective in fostering functional neuromotor recovery. The identification of a safe, cost-effective approach, such as forced aerobic exercise, to augment the recovery of function post-stroke would reduce the cost associated with intensive rehabilitation while simultaneously decreasing the cardiovascular risk factors prevalent in stroke survivors. Animal and human literature reveal that acute bouts of high-rate aerobic exercise results in increased concentrations of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF). These neurotrophic factors have been implicated as the mechanism that promotes neuroprotection, neurorecovery, and neuroplasticity. Clinical improvements in motor and cognitive function have been reported as a result of intensive aerobic exercise training, hypothesized to be due to this endogenous release of neurotrophins. These global changes in neurologic function have not been reported in patients with stroke. The PIs hypothesize that the pathophysiology of stroke, which limits sustained high rate and high intensity exercise, prevents the endogenous release of these neurotrophic factors. The PIs developed a safe lower extremity forced exercise intervention in Parkinson's disease (PD) patients that allows them to achieve an exercise rate greater than their voluntary rate. Following an eight week forced exercise intervention, PD patients exhibit significant improvements in global motor functioning, fine motor upper extremity function, cognition and olfaction. Based on fMRI data, acute forced exercise in PD patients indicates a similar pattern of cortical and subcortical activation between forced exercise and antiparkinsonian medication, suggesting forced-exercise does alter brain function. To investigate the effects of aerobic exercise on the recovery of function in stroke patients, a two year, single-center, parallel-group, rater-blind preliminary study is proposed. A total of 30 chronic (6-12 months post) stroke patients with residual hemiparesis will be randomized to one of three groups: combined forced-exercise and repetitive task practice (FE+RTP), combined voluntary exercise and repetitive task practice (VE+RTP) or a dose-matched RTP only (RTP only) group. All three groups will receive an identical dose of rehabilitation time over a course o 8 weeks (3X per week); however, the combination groups will perform forced or voluntary exercise for 50% of the session and RTP for the remaining 50% of the session. The RTP only group will engage in RTP exclusively. Outcomes will be gathered at baseline, mid-treatment and end of treatment (EOT). It is hypothesized that the forced-exercise intervention will serve to prime the central nervous system resulting in improved clinical outcomes for the FE+RTP group. Comparable improvements in aerobic capacity are expected for both exercise groups. If forced exercise is shown effective, it could become a viable adjunct to current neurorehabilitation approaches in driving neural recovery while simultaneously improving cardiovascular health. PUBLIC HEALTH RELEVANCE: Current approaches to stroke rehabilitation involve intensive, therapist-directed task practice that is expensive and in some cases ineffective in fostering functional neuromotor recovery. The identification of a safe, cost-effective approach, such as forced aerobic exercise, to augment the recovery of function post-stroke would reduce the cost associated with intensive rehabilitation while simultaneously decreasing the cardiovascular risk factors prevalent in stroke survivors. The PIs have developed a safe lower-extremity forced exercise intervention for patients with Parkinson's disease that has been shown to improve global motor function, cognition and olfaction. These changes coupled with functional magnetic resonance imaging patterns suggest that forced-exercise may be altering brain function. The PIs are proposing to conduct a preliminary study to investigate the effects of forced versus voluntary-rate aerobic exercise on the recovery of neurologic function in patients with stroke. Identifying the relationship between aerobic exercise (forced or voluntary) and the recovery of motor and non-motor function post-stroke will serve to optimize current neurorehabilitation approaches.